Jiabao Liu
The First Affiliated Hospital of Nanjing Medical University, China
Title: Epicardial injection of Ad-HGF activates endogenous c-kit+ cardiac stem cells and fosters survival and regeneration of the infarcted rat heart
Biography
Biography: Jiabao Liu
Abstract
Ischemic heart disease is the leading cause of morbidity and mortality worldwide due to the inability of the heart to replace lost myocytes. While the discovery of c-kit+ cardiac stem cells (CSCs) provides us a new opportunity to repair the damaged heart, the proliferation, differentiation and regulation of the CSCs remains elusive. Therefore, here we investigated whether adenovirus vector containing hepatocyte growth factor gene (Ad-HGF) can promote the proliferation and differentiation of c-kit+ CSCs into cardiomyocytes, smooth muscle cells or endothelial cells. We firstly discovered a positive correlation between the expression levels of HGF and c-kit+ CSCs among neonatal, adult and senior SD rats in vivo. Notably, epicardial injection of Ad-HGF following MI activates c-kit+ CSCs and promotes proliferation and differentiation into cardiomyocyte, endothelial cell and smooth muscle cell in vivo. Ad-HGF treatment promotes angiogenesis, inhibits fibrosis and improves the cardiac function of the rat following MI. The protective role of HGF may be due to the activation of c-Met receptor, and subsequent activation of the p-Akt-p21/p27-cell cycle pathway. Meanwhile, the levels of Bcl-2/Bcl-xL were elevated, while the levels of cleaved caspase 3 and Bax were reduced. Taken together, Ad-HGF promotes heart repair by regulating c-kit+ cardiac stem cell proliferation and differentiation and prevents heart failure following MI. This approach may provide new strategy for the treatment of ischemic heart disease.